Attempts to implant various cells have been made in order to repair damaged tissues. For example, in order to repair cardiac muscle tissues damaged by ischemic heart disease such as angina pectoris and myocardial infarction, it has been attempted to use fetal cardiac muscle cells, skeletal myoblasts, mesenchymal stem cells, cardiac stem cells, and ES cells (See, for example, Haraguchi et al., Stem Cells Transl Med. 2012 February; 1(2): 136-41).
As part of the attempts, a cell structure formed using a scaffold and a sheet-shaped cell culture, which is a sheet of cells, have been developed (See, for example, JP-T-2007-528755).
With respect to therapeutic applications of a sheet-shaped cell culture, use of a cultured epidermal sheet for skin injuries such as a burn, use of a corneal epithelial sheet-shaped cell culture for corneal injuries, and use of an oral mucosal sheet-shaped cell culture for endoscopic resection of esophageal cancer have been investigated.
In order that a sheet-shaped cell culture engrafts in the recipient tissue and carries out a desired function, it is necessary that oxygen and nutrients are supplied to the culture, and it is known that for this, effects of various cytokines such as HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor) which have an angiogenic effect can be useful (See, for example, JP-T-2007-528755).
Therefore, the engraftment rate of a sheet-shaped cell culture and its functionality, can be improved when the cytokine productivity of the sheet-shaped cell culture are improved. In addition, it is known that these cytokines are useful for the regeneration of tissues (See, for example, Nakagami et al., J Atheroscler Thromb. 2006 April; 13(2): 77-81), and thus when the cytokines produced by a sheet-shaped cell culture act on the recipient tissue, the regeneration of the tissue can be promoted. However, no low-cost methods for improving the cytokine productivity of a sheet-shaped cell culture are known.